Chronic kidney disease (CKD) results from diseases including diabetes and hypertension. In CKD, renal fibrosis progresses gradually and irreversibly, leading to an eventual loss of renal functions. CKD patients are diagnosed with end-stage renal disease when the condition progresses to a point where only 15% or less of renal functions remains. Treatment of end-stage renal disease requires renal replacement therapy and often requires hemodialysis as well. Hemodialysis therapy has the following problems: it takes several hours per session, about three sessions per week, which leads to a significant decrease in quality of life (QOL); it induces complications when the therapy continues for a prolonged period of time; and it incurs high medical expenses for life-long treatment, which has become a social issue. To avoid the need for hemodialysis or peritoneal dialysis therapy, patients with end-stage renal disease require kidney transplantation. However, there is a serious shortage of kidney donors worldwide including in Japan, and therefore these conventional therapies need to be replaced by a new one. It is an urgent matter to inhibit the progression of CKD conditions for reducing the frequency of conducting dialysis therapy.
Attempts have been made to inhibit CKD progression by treating the primary diseases. However, no direct treatment of the kidneys themselves has been established. Cytokines such as an HGF were studied for their action to inhibit progression of renal fibrosis (NPLs 1 and 2, for example). However, the cytokines are lost upon systemic administration by substantial proportions due to first-pass effect in the liver, making it difficult to retain effective concentrations of the cytokines to act on the kidneys for an extended period of time (NPL 3).